Activating transcription factor 3 enhances chemosensitivity of dichloroacetic acid via p53 pathway in cervical squamous epithelial cancer cells

Purpose: To investigate the effect of activating transcription factor 3 (ATF) on dichloroacetic acid (DCA) for the treatment of cervical cancer.Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry assays were first used to determine the effect of DCA treatment on SW756 cells. Next, western blotting was performed to test apoptotic markers and activating transcription factor 3 (ATF3) expression. MTT and flow cytometry assays were conducted to test the effect of ATF3 on the viability and apoptosis of cervical cancer cells. Finally, western blotting, quantitative real-time polymerase chain reaction (qRTPCR), and flow cytometry assays were used to examine the causality between ATF3 and P53.Results: The expression of ATF3 was significantly upregulated (p < 0.001) in cervical cancer cells treated with DCA. ATF3 overexpression consolidated the suppressive effect of DCA on cell proliferation and induced apoptosis (p < 0.001), suggesting that tumor protein 53 (P53), a tumor suppressor, was responsible for ATF3-mediated anti-tumorigenesis in DCA-treated cervical cancer.Conclusion: These results indicate that ATF3/P53 signaling is critical to treating cervical cancer with DCA and provides new insights into cervical cancer diagnosis, treatment and prognosis.Keywords: Cervical squamous epithelial cancer, Activating transcription factor, Tumor protein 53 (P53), Tumor suppressor, Dichloroacetic aci